View source for 3bkd

==High resolution Crystal structure of Transmembrane domain of M2 protein==
<StructureSection load='3bkd' size='340' side='right' caption='[[3bkd]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bkd]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BKD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bkd RCSB], [http://www.ebi.ac.uk/pdbsum/3bkd PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/Q9Q0P0_9INFA Q9Q0P0_9INFA]] Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry.[RuleBase:RU361247]  Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation.[SAAS:SAAS00108379] 
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== Publication Abstract from PubMed ==
The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.

Structural basis for the function and inhibition of an influenza virus proton channel.,Stouffer AL, Acharya R, Salom D, Levine AS, Di Costanzo L, Soto CS, Tereshko V, Nanda V, Stayrook S, DeGrado WF Nature. 2008 Jan 31;451(7178):596-9. PMID:18235504<ref>PMID:18235504</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Avian Influenza Neuraminidase%2C Tamiflu and Relenza|Avian Influenza Neuraminidase%2C Tamiflu and Relenza]]
*[[Ion channels|Ion channels]]
*[[M2 protein|M2 protein]]
*[[Proton Channels|Proton Channels]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acharya, R]]
[[Category: Salom, D]]
[[Category: Stouffer, A L]]
[[Category: Influenza a virus m2 protein]]
[[Category: M2tm]]
[[Category: Membrane protein]]
[[Category: Proton channel]]
[[Category: Viral protein]]